Steroidal compounds and methods for obtaining the same



Patented Oct. 8, 1946 STEROIDAL COMPOUNDS FOR OBTAINING THE Romeo B. Wagner, State College, Pa., assignor to AND METHODS SAME Parke, Davis & Company, Detroit, Mich., a corporation of Michigan No Drawing. Application May 15, 1944, Serial No. 535,757

This invention relates to the preparation of new pseudo-sapogenins from new steroidal sapo enins some of which are described in my copending application, Serial No. 530,758, filed May 15, 19%. (See also J. Am. Chem. Soc. 65, 1199 (1943).) These compounds are valuable as intermediates for the preparation of hormones of the sex hormone type and particularly of the adrenal cortex hormone type since they are oxygentated at position 12 of the steroid nucleus.

The reaction by which steroidal sapogenins are isomerized to. the pseudo-genins have been described in detail in the copending Patents Nos. 2,352,848 and 2,352,852, issued July 4, 1944. These also include proof of structure of the pseudogenin side chain.

This invention relates to the preparation of pseudo-genins having the formula Y CH3 omen,

. DEL (Em where Y is or a group hydrolyzable to H where Y is a member of the class groups hydrolyzable to H and =0 and Y is a member of the class OH and groups hydrolyzable to OH.

Specific examples of this type compound are pseudo-hecogenin in which Y at 3 is Y at 12 is =0, Y at 27 is OH, and the configuration at 0-5 is allo. In pseudo-hecogenin di- 9 Claims. (Cl. 260239.5)

acetate both hydroxyls are acylated by acetyl groups. Similarly pseudo-rockagenin has .the allo configuration at C-5 and hydroxyls at 3, 12 and 27. Pseudo-furcogenin is, however, of the regular configuration at C-5 and carries hydroxyls at C-3 and 27 with a ketone group at (3-12.

The invention may be illustrated by the following example:

Pseudohecogenin.--A sealed tube containing 5 g. of hecogenin and 15 cc. .of acetic anhydride was heated at 200 for 10 hours. The solvent was removed in vacuo and the solid residue was treated with a solution of 5 g. of potassium hydroxide in 500 cc. ethanol for thirty minutes. The product was ether extracted and the ethereal solution was washed and evaporated. The acetone solution of the residue after treatment with Norite was concentrated and cooled to give white needles,'M. P. 189-191; yield 2.6 g.

Anal.: Calcd for Cal-14204: C, 75.3; H, 9.8. Found: C, 75.2; H, 9.9.

While for ease of manipulation and economy the preferred isomerizing agent is acetic anhydride other lower aliphatic acid anhydrides may also be used. The preferred temperature range lies between 190 and 200 C. although the reaction also takes place as low at or as high as 230. The example is intended as illustrative and the invention is not necessarily limited to the conditions and reactants therein cited.

The above mentioned transformations can be illustrated diagrammatically as follows:

0 CH; CHr-CH: CH5 CH: 2}

11-0 CHI-CH! Hecogenin Acyl anhydride at 200 (e. g. acetic anhydride) 0. for 10 hours Pseudo hecogenin dlacylate (e. g. diacetate) Acyl anhydride (0. g. acetic anhydrlde) at 200 0. for about 10 hours.

H1O Ac Pseudo-furcogenin diacylate (e. g. diaeetate) In addition to using ethanolic KOH solution for hydrolyzing the acylated pseudogenin to the free genin, one can use any other suitable alka-' line solution, for example one containing NaOH, K2CO3, KHCOs, NazCOa, NaHCOa or the like, If an alcohol is required to aid hydrolysis, this can be methanol or other lower aliphatic alcohol instead of ethanol.

What I claim is:

1. A pseudo-sapogenin formula compound 0; the

Ylli/ where Y and Y" are members of the class and groups hydrolyzable to and Y is a member of the class 0, v I,

and groups hydrolyzable to lAlkalinehydrolysis 0 CH: CHz-CH; CH! CH1 1: 5

=0 OH-CH:

H OH I 2 AN H k m) Pseudo hecogenin ,7

H0 CH CH CH: /CH:CH:

a JlH-C\ (EH-CH;

o o, H V

V N H Id Rockogemn Ac lanh dride (e. acetic anhydride) l y at 2 60" OJm-everal hours.

A00 CH CH (EH: /CH2|CH2 3 C=C CH-CH;

CH 0A0 I \H l 2 H 7 A00 4 is:

Pseudo-rockogenin triacylate (e. g. triacetate) 1 Alkaline hydrolysis H0 ,CH CH CH: /CH:CH!

o=o CH-CH:

HIOH

Pseudo-rockogenin CH o CH cm cm-om $H CHCH;

\Hl O C H Furcozenln 5 6 2. A pseudo-sapogenln compound of the for- CH CH mula' z o=o-oH,oH1

Y CH; omen, CHa CHs (IJ H-CH:

H-CH: H |CH=Y O H=Y v H H W i "V where Y, Y and Y" are members of the class where Y, Y and Y" are each members of the class H and H 6. A: pseudo-furcogenm compound or the H formula, v

0 0H: and groupshydrolyzable to I OH H-CH:

CH=Y H 3. A pseudo-sapcgenln compound of the formula k CH Y CH (111: /CH2CH2 1'1 )k a 0:0 H-cm Where Y and Y are members of the class JH=Y 0H (Pam H and H '7. Pseudo-hecogemn havmg the formula,

where Y and Y" are each members of the class and groups hydrolyzable to 8. Pseudo-rockogenin having the formula,

4. A pseudo-hecogenin compound of the formula O CH: OH; H OH: I

C==CCH:CH2

(DEF-CH:

CH=Y

where Y and Y" are members of the class and H H 5. A pseudo-rockogenin compound of formula,

HO- l I 9. Pseudc-furcogenln having the formula,

the

O CH:

\Ji CH-CH: 

